Nevus cells exhibit growth characteristics in culture which differentiate them from melanocytes and melanoma cells. We examined the expression of c-jun, c-fos and jun-B mRNA levels in cultures of different melanocytic cell types to determine if biologic differences among these cells was due to their level of proto-oncogene expression. Because cell growth and differentiation are also known to be affected by serum conditions, the expression of c-jun, c-fos and jun-B was examined under normal serum conditions and serum starved and repleted conditions which stimulates proto-oncogene expression. Expression of c-jun and jun-B was not significantly different among the cell types studied under normal serum conditions, or serum starved and refed conditions and c-fos was not detectable in any of the unstimulated cell types. In contrast, when the cells were serum starved and refed, the level of c-fos expression was uniformly increased (2-10 fold) in 3 different nevus cell lines. This increase was not seen in normal melanocyte cultures or 2 melanoma cell lines. With serum deprivation and repletion, c-fos was also elevated in 1 melanoma cell line. We conclude that the regulation of the proto-oncogene c-fos is different in nevus cells than in normal melanocytes, which may contribute to the different growth characteristics seen with nevus cells.